基因检测在Ⅳ型埃勒斯-当洛综合征诊断中的意义

目的 埃勒斯-当洛综合征(Ⅳ型)是临床罕见病例,诊断困难,基因检测技术可明确该病诊断.方法 设计Col3A1基因引物,提取患者外周血标本DNA,PCR扩增后行测序分析碱基突变点,确认氨基酸变化位置,结合临床特征进行疾病诊断.结果 患者Col3A1基因外显子30的第2209个碱基及内含子15的第327碱基出现套峰.在2209位碱基出现G-A的突变,造成第698个氨基酸变化,由丙氨酸(Ala)改变为苏氨酸(Thr),即:P.A698T(c.2209G＞A),突变来源于先证者家系.结论 基因检测可以明确埃勒斯-当洛综合征诊断,对临床有指导意义.

Abstract：

Objective To ascertain the diagnosis of such a rare disease as Ehlers-Danlos syndrome type Ⅳ by the technique of DNA(deoxyribonucleic acid)analysis.Methods The primer sequences of Col3A1 gene were designed. Genomic DNA was isolated from the peripheral blood samples. The amplification of polymerase chain reaction(PCR)was performed and direct sequencing used to screen the mutations.A definite diagnosis was made in conjunctions with clinical features.Results Two nucleotide mutations for Col3A1 were found. One was in intron 15 while another in exon 30. The latter was an important mutation of a G to A transition(c.2209G＞A)resulting in alanine to threonine substitution at position(p.Ala698Thr).The mutations were inherited from proband of pedigree.Conclusion Genetic testing of Col3A1 mutation can facilitate an accurate diagnosis of Ehlers-Danlos syndrome.     

Wntless spatially regulates bone development through β‐catenin–dependent and independent mechanisms

Background : Canonical and noncanonical Wnt signaling pathways both play pivotal roles in bone development. Wntless/GPR177 is a chaperone protein that is required for secretion of all Wnt ligands. We previously showed that deletion of Wntless within mature osteoblasts severely impaired postnatal bone homeostasis. Results : In this study, we systemically evaluated how deletion of Wntless in different stages of osteochondral differentiation affected embryonic bone development, by crossing Wntless (Wls)‐flox/flox mice with strains expressing cre recombinase behind the following promoters: Osteocalcin, Collagen 2a1, or Dermo1. Ex vivo µCT and whole‐mount skeletal staining were performed to examine skeletal mineralization. Histology and immunohistochemistry were used to evaluate cellular differentiation and alterations in Wnt signaling. In this work, we found that Wntless regulated chondrogenesis and osteogenesis through both canonical and noncanonical Wnt signaling. Conclusions : These findings provide more insight into the requirements of different Wnt‐secretion cell types critical for skeletal development. Developmental Dynamics 244:1347–1355, 2015. © 2015 Wiley Periodicals, Inc.     

The Heart in Diabetic Ketoacidosis: A Narrative Review Focusing on the Acute Cardiac Effects and Electrocardiographic Abnormalities

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus. Hyperglycemia, acidosis, and electrolyte imbalances can directly affect the heart by inducing toxicity, impairing myocardial blood flow, autonomic dysfunction, and altering activation and conduction of electrical impulses throughout the heart, increasing the risk of arrhythmias and ischemia. The electrocardiogram is useful in monitoring patients during and after an episode of DKA, as it allows the detection of arrhythmias and guides metabolic correction. Unfortunately, reports on electrocardiographic abnormalities in patients with DKA are lacking. We found two electrocardiographic patterns that are frequently reported in the literature: a pseudo-myocardial infarction and a Brugada Phenocopy. Both are associated with DKA metabolic anomalies and they resolve after treatment. Because of their clinical relevance and the challenge they represent for clinicians, we analyzed the clinical characteristics of these patients and the mechanisms involved in these electrocardiographic findings.     

川芎嗪对动脉球囊损伤后胶原合成的影响

目的研究川芎嗪（TMP）对大鼠颈动脉球囊损伤后胶原合成的影响及机制。方法建立大鼠颈动脉球囊损伤模型,分为假手术组、模型组、TMP组。TMP组大鼠尾静脉预给药10mg/（kg·d）1周,球囊成形术后继续同剂量TMP尾静脉注射6周,模型组球囊成形术后予等容积0.9%氯化钠溶液尾静脉注射6周。假手术组仅行右颈外动脉切开,不插入球囊导管进行损伤内膜操作。各组于第6周收集损伤段颈动脉,病理切片苦味酸天狼星红胶原特异染色及Western blot检测相关蛋白表达水平。结果大鼠颈动脉球囊损伤后6周,模型组内膜胶原容积积分（CVF）较假手术组增加,而TMP组CVF比模型组减少（均P＜0.05）;与假手术组比较,模型组损伤段血管Wnt4、Dvl-1、β- catenin、CyclinD1表达水平增高,而TMP组表达减少（均P＜0.05）;模型组胶原Col-1、Col-3的表达水平高于TMP组（P＜0.05）。结论 TMP可以抑制大鼠颈动脉球囊损伤后胶原增生,其机制与下调wnt信号通路有关。